1. Field of the Invention
The present invention relates to an apparatus for a diagnosis and therapy utilizing an ultrasound, and particularly, to the apparatus for the diagnosis and therapy utilizing the ultrasound used in combination with a phase-shift type ultrasound contrast agent.
2. Description of the Related Art
It is a long time since image diagnostic modalities such as an X-ray CT (Computed Tomography) apparatus, an MRI (Magnetic Resonance Imaging) apparatus, and an apparatus for a diagnosis and therapy became an indispensable tool in clinical settings. These are something where differences of a CT value, a spin relaxation time, and an acoustic impedance within a living body are imaged, respectively, and are called “anatomical imaging” because the differences of these physical properties mainly reflect a living orgasm. On the other hand, something for imaging a target position of a functionally different state is called “functional imaging” even if it is a structurally same tissue.
Out of the functional imaging, for example, something for visualizing an existing state of a living body constitutional molecule such as a protein, an amino acid, and a nucleic acid is called “molecular imaging” in may cases. The molecular imaging is one of research areas that currently get most attention because an application to an elucidation of a life process such as a generation and differentiation and to a diagnosis and therapy of a disease is expected.
As image diagnostic modalities specialized in such the molecular imaging can be cited a PET (Positron Emission Tomography) apparatus and an optical imaging apparatus. The former is broadly used as a tool for classifying a clinical widening extent and proceeding stage of a tumor; the latter as a noninvasive analysis tool of a drug in such a drug development where a small animal is used.
In addition, also in modalities such as the MRI and the ultrasonic apparatus for the diagnosis and therapy where an application as the morph imaging is precedent, a research and development for utilizing them as the molecular imaging progresses.
Furthermore, the ultrasonic apparatus for the diagnosis and therapy is expected as a diagnosis and therapy integration tool usable other than in a big hospital because it has features, which other modalities do not have, such as being 1) excellent in real time property, 2) less in restriction with respect to a use within an operation room thanks to its smallness, and 3) also usable as a therapeutic tool as well as a diagnostic tool.
Here, a therapeutic method of using an ultrasound can be mainly classified into two. One is a thermal coagulation therapy that converges and exposes the ultrasound, heats up a target position not less than a protein denaturation temperature (about 65 degrees Celsius) in a short time of a few seconds, and thereby, treats the target position. Because the thermal coagulation therapy is a therapy of using a high intensity focused ultrasound (HIFU) not less than 1 kW/cm2, it is called an “HIFU” therapy in many cases.
However, if because the HIFU therapy obtains an exposure positional selectivity only due to a convergence of an ultrasound, an aim is missed due to a body movement, there is a possibility that a high intensity ultrasound not less than 1 kW/cm2 is exposed on a target position other than a target position. Therefore, it is preferable that a therapeutic method has the positional selectivity other than the convergence of the ultrasound.
Another therapeutic method for using an ultrasound is a therapy by (acoustic) cavitation action. A cavitation is basically a phenomenon that a bubble nucleus is produced by ultrasound, the bubble grows, and is collapsed. Because if the cavitation occurs, a high temperature of several thousand degrees and a high pressure of several hundreds occur at the collapse stage of a last bubble, it is enabled to treat a target position, utilizing this. Furthermore, it is enabled to more effectively treat the target position by a chemical substance called an acoustic chemical active substance activated by cavitation (for example, see a pamphlet of WO 98/01131).
In any one of the therapeutic methods for using an ultrasound, it is preferable to reduce an ultrasound exposure amount in order to alleviate a burden of an inspected body. Consequently, in order to restrict an exposure range, a method of properly identifying a tumor position is requested.
In general chemical and radio active therapy fields are disclosed methods of utilizing a “molecular probe” for selectively bonding a living body constitutional molecule such as an antibody and a ligand, detecting a tumor, and making the tumor a therapy target (for example, see pages 750-763 in Cancer 2 (Nature Rev. 2) by Allen (2002)). These tumor identification methods are also utilized for an ultrasonic contrast agent used for an ultrasonic apparatus for a diagnosis and therapy.
In addition, if there exist a micro bubble used as an ultrasonic contrast agent, it is well known in exposing an ultrasound that an apparent absorption coefficient becomes higher (for example, see pages 1399-1412, Ultrasound Med. Biol 27 by Holt et al. (2001)). Because if it is possible to restrict the micro bubble only to a target position, it is enabled to selectively heat up the target position with using the phenomenon, it is enabled to reduce an ultrasound exposure amount in a thermal coagulation therapy.
In addition, an existence of a micro bubble in an ultrasound exposure position corresponds to a stage that the bubble on the way of a cavitation process has grown, and it is possible to omit one step of a nucleus production requested for a production of a cavitation by exposing an ultrasound at the stage. Therefore, it is well known that an acoustic intensity requested for the production of the cavitation is reduced by the existence of the micro bubble (for example, see pages 2059-2069 in J. Acoust. Soc. Am. 88 by Holland et al. (1990)). In other words, if it is possible to restrict a micro bubble to a target position, with using the phenomenon it is enabled to reduce an ultrasound exposure amount in a therapy by cavitation action.
However, because a micro bubble cannot exist only in a blood vessel due to a restriction of a size thereof, it is difficult to restrict the bubble to a specific position of a tissue.
Consequently, a phase-shift type ultrasound contrast agent is disclosed that is a droplet of a nano size when dosed in a living body, produces a phase shift by ultrasound exposure, and thereby produces a micro bubble (for example, see Ultrasound Contrast Image 92 (Proc. 4th Intern Symp.) by Kawabata et al. (2004)). It is possible to move the droplet of the nano size if any to a tissue such as a tumor, and furthermore, it is possible to make the droplet have a tissue selectivity by adding the molecular probe. Ultrasound imaging higher in tissue selectivity is enabled by using such a phase-shift type ultrasound contrast agent.
Meanwhile, it is disclosed that in order to stably causing a phase shift of such a phase shift ultrasound contrast agent is requested a temporally averaged acoustic intensity surpassing 0.72 W/cm2 of an upper limit usable in a usual ultrasonic apparatus for a diagnosis and therapy (for example, see Ultrasound Contrast Image 92 (Proc. 4th Intern Symp.) by Kawabata et al. (2004)).
In addition, as a new diagnostic modality for using an ultrasound is disclosed radiation pressure imaging (for example, see pages 1087-1093 in Trans. IEEE Medical Imag. 23 by Alizards et al. (2004)). In the Medical Imag. 23 is proposed the diagnostic modality for performing a diagnosis, using an ultrasound not less than an acoustic intensity restricted in a conventional ultrasonic apparatus for a diagnosis and therapy.
By combining the phase-shift type ultrasound contrast agent and an ultrasound therapy, it is enabled to restrict a micro bubble to a target position and to reduce an ultrasound exposure amount in the ultrasound therapy.
As described above, because a micro bubble is produced in making an image, using the phase-shift type ultrasound contrast agent, it is enabled to apply the contrast agent to a therapy as well as a diagnosis.
However, because a conventional ultrasonic apparatus for a diagnosis and therapy cannot start a therapy in conjunction with the production of a micro bubble from the phase-shift type ultrasound contrast agent, there is a problem that an ultrasound of a comparatively high intensity is requested to be exposed in producing the micro bubble from the contrast agent.
Consequently, an ultrasonic apparatus for a diagnosis and therapy is strongly requested that can perform the therapy in conjunction with making imaging by a phase-shift type ultrasound contrast agent.